The term overlap syndrome (OS) is used to describe the association of both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea disease (OSA) in a single Veteran. Given the high prevalence of both COPD and OSA, it is expected that a third of Veterans with OSA could be affected by OS. We demonstrated in 2 cross-sectional studies that the prevalence of OS in our Veteran population with COPD was above 44%. Importantly, Veterans with OS have a higher cardiovascular morbidity and mortality than either OSA or COPD-only Veterans, likely due to worse nocturnal hypoxia and subsequent inflammation and endothelial dysfunction. Our preliminary data shows that serum hs-CRP levels are higher in Veterans with OS than Veterans with COPD-only. Therefore, therapy for Veterans with OS that decreases cardiovascular disease (CVD) by targeting inflammation is a high priority. Home-based exercise interventions that translate to a lifestyle with increased physical activity (PA) are an ideal strategy as 150 minutes of leisure time PA a week is associated with reduction in risk of CVD-related events and death. Further, PA decreases biomarkers of systemic inflammation (IL-6 and CRP). However, no data is available on the effect of exercise on biomarkers of systemic inflammation in Veterans with OS. It is difficult to increase the leisure time PA in adults with COPD and OSA as this population is more sedentary due to a combination of increased obesity, daytime sleepiness and dyspnea. Therefore, home-based exercise would be ideal for these Veterans. In a pilot study of 19 Veterans with COPD we demonstrated that the use of the Wii Fit program for home-based exercise was feasible and safe. The mean six-minute walk distance increased by 23 meters (p=0.01) after 12 weeks of moderate intensity exercise with the Wii Fit. Thus, adapting this exercise strategy to Veterans with OS is a novel treatment approach whose goal is durable increases in leisure time PA. Randomized controlled trials have failed to demonstrate that the current standard therapy for OSA, i.e. continuous positive airway pressure (CPAP), alters inflammatory markers in OSA. The objective of this proposal is to conduct a single arm 12- week home-based exercise pilot intervention to determine the effect on biomarkers of systemic inflammation in 50 Veterans with OS on CPAP. We hypothesize that 1) Baseline PA intensity and duration will correlate inversely with the biomarkers of systemic inflammation independently of nocturnal hypoxia; and 2) Exercise training using a home-based computer exercise program will decrease biomarkers of systemic inflammation and increase exercise capacity in Veterans. To test these hypotheses, we will analyze measures of baseline PA intensity and duration (accelerometry) and biomarkers of systemic inflammation in Veterans with OS (AIM 1). Then the following parameters will be assessed at baseline and after 12 weeks of home exercise training: a) biomarkers of systemic inflammation; b) PA intensity and duration; c) exercise capacity (AIM 2). Findings will support a future randomized exercise trial that will impact strategies to reduce CVD risk and in Veterans with OS through increased physical activity. The long-term clinical goal is to successfully implement a home exercise intervention in the routine medical care of the large Veteran population with sleep disordered breathing (SDB) with the ultimate goal of reducing their risk of CVD-related events and death through increased physical activity. This research area is a high priority given the high prevalence of OS and impact on Veterans' and general population morbidity, mortality and health-care associated costs.